Reaction Steps
and 1-(4-((S)-8-(cyanomethyl)-4-((S)-3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea (xq2): Tert-butyl 8-(cyanomethyl)-2-(4-(3-ethylureido)phenyl)-4-((S)-3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (0.599 g, 0.00112 mol) and 4.0 M of Hydrogen chloride in 1,4-Dioxane (8.5 mL) were combined and shaken for 2.5 hours then concentrated, diluted with sat NaHCO3, extracted three times with 10% MeOH in dichloromethane, dried over Magnesium sulfate, filtered, concentrated, purified by HPLC, and the diastereomers were separated by SFC. R Diastereomer (xq1): 1H NMR (400 MHz, DMSO) δ 8.65 (s, 1H), 8.21 (d, J=8.7, 2H), 7.48 (d, J=8.7, 2H), 6.16 (t, J=5.6, 1H), 4.21-4.05 (m, 2H), 3.89 (d, J=11.0, 1H), 3.75 (d, J=9.1, 1H), 3.60 (dd, J=20.1, 9.2, 2H), 3.54-3.38 (m, 2H), 3.19-3.02 (m, 5H), 2.83-2.63 (m, 2H), 2.55-2.39 (m, 2H), 1.17 (d, J=6.6, 3H), 1.06 (t, J=7.2, 3H). LC/MS-m/z+436.2 (M+H)+; S Diastereomer (xq2) 1H NMR (400 MHz, DMSO) δ 8.64 (s, 1H), 8.21 (d, J=8.7, 2H), 7.47 (d, J=8.7, 2H), 6.15 (t, J=5.5, 1H), 4.09 (d, J=5.9, 2H), 3.87 (d, J=10.4, 1H), 3.74-3.57 (m, 4H), 3.38 (t, J=10.6, 1H), 3.16-2.98 (m, 5H), 2.78 (d, J=8.1, 1H), 2.69 (d, J=14.5, 1H), 2.57-2.39 (m, 2H), 1.32 (d, J=6.6, 3H), 1.06 (t, J=7.2, 3H). LC/MS-m/z+436.2 (M+H)+.
